This research project is an attempt to clarify the involvement of airway smooth muscle in the experimental model of airway hyperreactivity. This research effort will address this issue in three different directions. First, we will establish experimental models of airway reactivity and we will establish the degree of airway reactivity using an inhalation challenge of histamine and methacholine. Second, this project will identify and define functional alterations of airway smooth muscle from animals with different types of airway hyperreactivity. This will be done by studying contractile characteristics which include both isometric and isotonic contraction of isolated tracheal and bronchial segments. A detailed evaluation of the length-tension and force-velocity relationships will also be done. The electrophysiological properties of airway smooth muscle will be studied as well. These studies will include the measurement of cable properties of normal and altered airway smooth muscle. Third, we will attempt to analyze the possible mechanism(s) of tissue alteration as found after acute sensitization and observed after repeated exposure of sensitizied animals to the inhalation challenge. We will examine the role of the Na+ electrogenic pump and relative ion permeabilities in this change of resting membrane potential. Response to different pharmacological agents which are established in these stimulatory and inhibitory actions as measured by both contractile and electrophysiological changes will be assessed. The issue of airway hyperreactivity is an important clinical issue frequently seen in several airway diseases. The understanding of its mechanism may lead to better and less empirical forms of therapy.